ObjectiveSubdural hematomas (SDH) account for an estimated 5 to 25% of intracranial hemorrhages. Acute SDH occur secondary to rupture of the bridging veins leading to blood collecting within the dural space. Risk factors associated with SDH expansion are well documented, however, there are no established guidelines regarding blood pressure goals in the management of acute SDH. This study aims to retrospectively evaluate if uncontrolled blood pressure within the first 24 h of hospitalization in patients with acute SDH is linked to hematoma expansion as determined by serial CT imaging.MethodsA single center, retrospective study looked at 1,083 patients with acute SDH, predominantly above age 65. Of these, 469 patients met the inclusion criteria. Blood pressure was measured during the first 24 h of admission along with PT, INR, platelets, blood alcohol level, anticoagulation use and antiplatelet use. Follow-up CT performed within the first 24 h was compared to the initial CT to determine the presence of hematoma expansion. Mean systolic blood pressure (SBP), peak SBP, discharge disposition, length of stay and in hospital mortality were evaluated.ResultsWe found that patients with mean SBP <140 in the first 24 h of admission had a lower rate of hematoma expansion than those with SBP > 140. Patients with peak SBP > 200 had an increased frequency of hematoma expansion with the largest effect seen in patients with SBP > 220. Other risk factors did not contribute to hematoma expansion.ConclusionsThese results suggest that blood pressure is an important factor to consider when treating patients with SDH with medical management. Blood pressure management should be considered in addition to serial neurological exams, repeat radiological imaging, seizure prophylaxis and reversal of anticoagulation.

Rationale Concern for drug-drug interactions leading to treatment failure and drug resistant strains have discouraged clinicians from attempting concomitant treatment of hepatitis C (HCV) and Tuberculosis. Increased metabolism of direct-acting antivirals (DAAs) by rifamycins has hindered concurrent use. Development of an assay for ledipasvir and sofosbuvir (LDV/SOF) serum concentrations for therapeutic drug monitoring (TDM) can ensure adequate therapy. Presented are the first cases of concomitant therapy of active TB and HCV with rifamycin containing regimens and DAAs using TDM. Objectives Using TDM, we aim to determine if concomitant therapy with rifamycin containing regimens and DAAs is safe and effective for patients co-infected with TB and HCV. Methods Five individuals with TB and HCV who experienced transaminitis prior to or during TB therapy, were concomitantly treated with rifamycin containing regimens and LDV/SOF. TDM was performed for ledipasvir, sofosbuvir and rifabutin during therapy. Baseline labs and serial liver enzymes were performed. HCV viral load and mycobacterial sputum cultures were obtained upon completion of therapy to determine efficacy of therapy. Measurements and Main Results All patients were found to have nondetectable HCV viral loads and negative mycobacterial sputum cultures upon completion of therapy. No clinically significant adverse effects were reported. Conclusions These cases illustrate concomitant use of LDV/SOF and rifabutin in patients with HCV/TB coinfection. Utilizing serum drug concentration monitoring to guide dosing, correction of transaminitis were achieved which allowed the use rifamycin containing TB therapy. These findings suggest that concomitant therapy of TB/HCV is possible, safe and effective.

The MTBDRplus assay (Hain Lifescience, Nehren, Germany) is a WHO-endorsed line probe assay for the detection of Mycobacteria tuberculosis (MTB), and mutations in genes associated with resistance to isoniazid (INH) and rifampin (RIF). This assay has been utilized in pulmonary specimens but there is little data to validate its use for extrapulmonary specimens. In 2009, the Florida Bureau of Public Health Laboratories adopted universal MTBDRplus assay testing of all diagnosed cases of tuberculosis, including extrapulmonary cases. This study analyzes the level of agreement between genotypic molecular testing by the MTBDRplus assay with conventional culture susceptibilities by mean inhibitory concentrations (MIC) on all confirmed MTB culture positive extrapulmonary cases in Florida in a one year timespan.

testing of all diagnosed cases of infection with Mycobacteria tuberculosis (MTB). This study analyzed the concordance of genotypic molecular testing by the MTBDRplus assay with conventional culture susceptibilities by mean inhibitory concentrations (MIC) on all culture-positive pulmonary MTB cases in Florida. METHODS: This was a retrospective, programmatic evaluation that used existing Florida Department of Health data on pulmonary specimens from 2014. Patient identifiers were removed. Of 452 cases of pulmonary tuberculosis, 270 were lacking data on either the MTBDRplus assay, or culture susceptibilities, and were excluded. 182 pulmonary specimens were used. Genotypic resistance to Rifampin (RIF), and Isoniazid (INH), was determined by detection of mutations in the rpoB, and katG or inhA genes, which are associated with resistance to RIF, and INH, respectively. RESULTS: There was concordance between rpoB gene mutation and RIF resistance in 3 of 3 cases. There was concordance between katG gene mutation and INH resistance (MIC >1 ug/mL) in 5 of 5 cases. Of patients who were found to have intermediate INH susceptibility (MIC >0.12 to <1 ug/mL), the mutation in inhA gene was found in 5 of 8 cases. There was no detectable mutation in 3 of 8 cases of intermediate susceptibility. We observe the positive predictive value of the MTBDRplus assay to be 100% and the negative predictive value to be 98%, overall. The median time from specimen collection to reporting for the MTBDRplus assay was 8 days. The median time from specimen collection to reporting for the conventional culture susceptibilities was 44 days. CONCLUSIONS: The MTBDRplus assay proved to be a reliable and timely method for accurate detection of Rifampin and Isoniazid resistance in routine clinical practice, but was not sensitive to reliably detect intermediate susceptibility to INH. One explanation for this is that the assay only probes for a portion of the inhA genes and there are mechanisms of low level resistance outside of the inhA genes. Further development of rapid molecular probes for intermediate susceptibility to INH are needed as this finding impacts the choice of treatment regimens. CLINICAL IMPLICATIONS: The MTBDRplus assay allows for efficient identification of definite cases of drug-resistant pulmonary tuberculosis. We advocate for its clinical use based on the ability to start effective, antitubercular treatment before the results of conventional culture susceptibilities are available.

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